| Affiliation: | 1. Behavioural Neurobiology Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada;2. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada;3. Centre of Neuromodulation, Hurvitz Brain Science Program, Sunnybrook Research Institute, University of Toronto, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada;4. Biopsychology Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada |
| Abstract: | BackgroundSome of the antidepressant-like effects of ventromedial prefrontal cortex (vmPFC) deep brain stimulation (DBS) in rodents have been attributed to the modulation of prefrontal-raphe pathways. This is largely different from selective serotonin reuptake inhibitors (SSRIs), which increase serotonin (5-HT) levels by inhibiting the serotonin transporter (SERT). SSRIs have limited efficacy when given to SERT knockout (KO) mice, or patients with mutations in the serotonin transporter promoter gene (5-HTTLPR).HypothesisvmPFC DBS will induce antidepressant-like effects and serotonin release in SERT KOs.ResultsDBS-treated wild-type and SERT KO mice had a significant 22-26% decrease in immobility in the forced swim test. DBS delivered to either group was associated with 33–55% increase in 5-HT levels.ConclusionsDBS induced a significant antidepressant-like effect in KO mice. This suggests that it may be reasonable to consider DBS in states where SERT is not fully operational. |
